Research in the pulmonary pathology laboratory has been focused upon the basic biological mechanisms through which inhaled particles cause lung disease. We have developed models of asbestosis and silicosis using rats and mice and have shown that the disease process is initiated at junctions of bronchioles and alveolar ducts. One hour of exposure to chrysotile asbestos is sufficient to cause progressive fibrogenesis at alveolar duct bifurcations. The process is initiated by a complement-dependent chemoattraction of lung macrophages to the sites of particle deposition. The central working hypothesis in our laboratory is that these macrophages synthesize and secrete an array of products which mediate the pathogenesis of lung fibrosis. For example, many of the metabolites of arachidonic acid are powerful inflammatory mediators and we have shown that these are synthesized and secreted by alveolar and intravascular macrophages. Also in the past year, we have shown that rat alveolar and interstitial macrophages synthesize and secrete a homologue of human platelet-derived growth factor (PDGF). This factor is a potent mitogen for mesenchymal cells, and we demonstrated that early passage fibroblasts from rat lungs exhibit specific receptors for the PDGF homologue. The degree of macrophage-derived PDGF secretion could be enhanced by treatment of the cells with a variety of stimulants including asbestos fibers, iron spheres, zymosan particles and bacterial lipopolysaccharide. Quantitative analysis of the PDGF was accomplished by eluting macrophage-conditioned medium through a high pressure liquid chromatograph at low pH. This allowed measurement of the PDGF in a competitive binding enzyme immunoassay developed in our laboratory. Studies are ongoing to establish whether or not this growth factor plays a mechanistic role in particle-induced lung fibrosis.